This proposal for a program project represents a multidisciplinary approach to the study of the basic biological effects of a variety of environmental agents. The research team consists of professionals trained in the fields of biochemistry, chemistry, engineering, oncology, physiology, pharmacology, toxicology, and medicine. There are included in the proposal (15) separate projects: 4 dealing with the effects of carbon monoxide, 3 with heavy metals (mercury, cadmium, and lead), 3 on basic studies of mutagenesis and carcinogenesis, and 5 on the response and defense of respiratory tract to environmental chemicals. It is felt that the basic scientific information that will arise from these studies will contribute greatly to the ability to make valid rational judgments concerning the health hazards of the many diverse chemical and biological agents to which man is being increasingly exposed. Such basic information is of absolute necessity for the setting of standards and for evaluating the complex parameters of the risk-benefit ratio.